Phospholipase C-δ1 and -δ3 are essential in the trophoblast for placental development

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in phosphoinositide turnover and is involved in a variety of physiological functions. We analyzed PLC delta 1 knockout mice and found that PLC delta 1 is required for the maintenance of skin homeostasis. However, there were no remarkable abnormalities except hair loss and runting in PLC delta 1 knockout mice, even though PLC delta 1 is broadly distributed. Here, we report that mice lacking both PLC delta 1 and PLC delta 3 died at embryonic day 11.5 (E11.5) to E13.5. PLC delta 1/PLC delta 3 double-knockout mice exhibited severe disruption of the normal labyrinth architecture in the placenta and decreased placental vascullarization, as well as abnormal proliferation and apoptosis of trophoblasts in the labyrinth area. Furthermore, PLC delta 1/PLC delta 3 double-knockout embryos supplied with a normal placenta by the tetraploid aggregation method survived beyond E14.5, clearly indicating that the embryonic lethality is caused by a defect in trophoblasts. On the basis of these results, we conclude that PLC delta 1 and PLC delta 3 are essential in trophoblasts for placental development.